The cellular mechanism of action of phorbol ester (PE) tumor promoters is being investigated in two model systems: 1) normal human peripheral blood lymphocytes in which PE's serve as costimulants with lectins to cause production of T cell growth factor (TCGF), and 2) Friend Erythroleukemia cells in which PE's inhibit the spontaneous or dimethylsulfoxide (DMSO) induced differentiation. Initial studies are being directed at identifying and characterizing specific PE receptors. Phorbol ester receptors have been identified in the lymphocyte system as judged by appropriate dose response curves, structure-activity relationships, and time courses for binding and TCGF production. Using PE sensitive and resistant clones of Friend cells, examination of the results of the phorbol ester-receptor interaction leading to the biological response will be expanded. Understanding the cellular mechanism of phorbol ester induced responses in these model systems should help explain the cellular mechanism(s) for tumor promotion and may suggest steps in the mechanism at which the response(s) can be inhibited.